Microsomal triglyceride transfer protein large subunit precursor

Names and origin

Protein names

Recommended name:
Microsomal triglyceride transfer protein large subunit

Gene names

Name:	MTTP
Synonyms:	MTP

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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Protein attributes

Sequence length	894 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

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General annotation (Comments)

Function	Catalyzes the transport of triglyceride, cholesteryl ester, and phospholipid between phospholipid surfaces. Required for the secretion of plasma lipoproteins that contain apolipoprotein B.
Subunit structure	Heterodimer composed of MTTP and of protein disulfide isomerase (P4HB/PDI) By similarity.
Subcellular location	Endoplasmic reticulum.
Tissue specificity	Liver and small intestine. Also found in ovary, testis and kidney. Ref.6
Induction	Positively regulated by cholesterol and negatively regulated by insulin. Ref.6
Involvement in disease	Defects in MTTP are the cause of abetalipoproteinemia (ABL) [MIM:200100]. ABL is an autosomal recessive disorder of lipoprotein metabolism. Affected individuals produce virtually no circulating apolipoprotein B-containing lipoproteins (chylomicrons, VLDL, LDL, lipoprotein(A)). Malabsorption of the antioxidant vitamin E occurs, leading to spinocerebellar and retinal degeneration. Ref.9 Ref.10 Ref.11
Sequence similarities	Contains 1 vitellogenin domain.

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Ontologies

Keywords
Biological process	Transport
Cellular component	Endoplasmic reticulum
Coding sequence diversity	Polymorphism
Disease	Disease mutation
Domain	Signal
Ligand	Lipid-binding
PTM	Disulfide bond
Technical term	Complete proteome
Gene Ontology (GO)
Biological process	lipid transport Inferred from electronic annotation. Source: InterPro
Cellular component	endoplasmic reticulum Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	lipid binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

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Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 18

18

Potential

Chain

19 – 894

876

Microsomal triglyceride transfer protein large subunit

PRO_0000041593

Regions

Domain

28 – 659

632

Vitellogenin

Natural variations

Natural variant

95

1

Q → H

VAR_014016

Natural variant

98

1

E → D: dbSNP rs2306986.

VAR_052961

Natural variant

128

1

I → T: dbSNP rs3816873. Ref.12 Ref.13

VAR_014017

Natural variant

166

1

N → S: dbSNP rs3792683.

VAR_052962

Natural variant

168

1

V → I Rare polymorphism. Ref.13

VAR_022658

Natural variant

244

1

Q → E: dbSNP rs17599091. Ref.12

VAR_014018

Natural variant

297

1

H → Q: dbSNP rs2306985. Ref.9 Ref.12 Ref.13

VAR_010640

Natural variant

354

1

E → Q: dbSNP rs12933.

VAR_014916

Natural variant

384

1

D → A: dbSNP rs17029215. Ref.9

VAR_010641

Natural variant

540

1

R → H in ABL; loss of activity. Ref.9 Ref.10

VAR_010642

Natural variant

590

1

S → I in ABL. Ref.10

VAR_010643

Natural variant

746

1

G → E in ABL. Ref.10

VAR_010644

Natural variant

780

1

N → Y in ABL; loss of activity. Ref.11

VAR_014019

Experimental info

Mutagenesis

540

1

R → K: No change of activity. Ref.9

Mutagenesis

878

1

C → S: Loss of activity. Ref.8

Sequence conflict

585

1

F → L in CAA42200. Ref.2

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Sequences

Sequence

Length

Mass (Da)

Tools

P55157-1 [UniParc].

Last modified October 1, 1996. Version 1.
Checksum: B20260C136BDAB9F
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FASTA

894

99,351

        10         20         30         40         50         60 
MILLAVLFLC FISSYSASVK GHTTGLSLNN DRLYKLTYST EVLLDRGKGK LQDSVGYRIS 

        70         80         90        100        110        120 
SNVDVALLWR NPDGDDDQLI QITMKDVNVE NVNQQRGEKS IFKGKSPSKI MGKENLEALQ 

       130        140        150        160        170        180 
RPTLLHLIHG KVKEFYSYQN EAVAIENIKR GLASLFQTQL SSGTTNEVDI SGNCKVTYQA 

       190        200        210        220        230        240 
HQDKVIKIKA LDSCKIARSG FTTPNQVLGV SSKATSVTTY KIEDSFVIAV LAEETHNFGL 

       250        260        270        280        290        300 
NFLQTIKGKI VSKQKLELKT TEAGPRLMSG KQAAAIIKAV DSKYTAIPIV GQVFQSHCKG 

       310        320        330        340        350        360 
CPSLSELWRS TRKYLQPDNL SKAEAVRNFL AFIQHLRTAK KEEILQILKM ENKEVLPQLV 

       370        380        390        400        410        420 
DAVTSAQTSD SLEAILDFLD FKSDSSIILQ ERFLYACGFA SHPNEELLRA LISKFKGSIG 

       430        440        450        460        470        480 
SSDIRETVMI ITGTLVRKLC QNEGCKLKAV VEAKKLILGG LEKAEKKEDT RMYLLALKNA 

       490        500        510        520        530        540 
LLPEGIPSLL KYAEAGEGPI SHLATTALQR YDLPFITDEV KKTLNRIYHQ NRKVHEKTVR 

       550        560        570        580        590        600 
TAAAAIILNN NPSYMDVKNI LLSIGELPQE MNKYMLAIVQ DILRFEMPAS KIVRRVLKEM 

       610        620        630        640        650        660 
VAHNYDRFSR SGSSSAYTGY IERSPRSAST YSLDILYSGS GILRRSNLNI FQYIGKAGLH 

       670        680        690        700        710        720 
GSQVVIEAQG LEALIAATPD EGEENLDSYA GMSAILFDVQ LRPVTFFNGY SDLMSKMLSA 

       730        740        750        760        770        780 
SGDPISVVKG LILLIDHSQE LQLQSGLKAN IEVQGGLAID ISGAMEFSLW YRESKTRVKN 

       790        800        810        820        830        840 
RVTVVITTDI TVDSSFVKAG LETSTETEAG LEFISTVQFS QYPFLVCMQM DKDEAPFRQF 

       850        860        870        880        890 
EKKYERLSTG RGYVSQKRKE SVLAGCEFPL HQENSEMCKV VFAPQPDSTS SGWF

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References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Abetalipoproteinemia is caused by defects of the gene encoding the 97 kDa subunit of a microsomal triglyceride transfer protein." Shoulders C.C., Brett D.J., Bayliss J.D., Narcisi T.M.E., Jarmuz A., Grantham T.T., Leoni P.R.D., Bhattacharya S., Pease R.J., Cullen P.M., Levi S., Byfield P.G.H., Purkiss P., Scott J. Hum. Mol. Genet. 2:2109-2116(1993) [PubMed: 8111381] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Small intestine.
[2]	"Cloning and gene defects in microsomal triglyceride transfer protein associated with abetalipoproteinaemia." Sharp D., Blinderman L., Combs K.A., Kienzle B., Ricci B., Wager-Smith K., Gil C.M., Turck C.W., Bouma M.-E., Rader D.J., Aggerbeck L.P., Gregg R.E., Gordon D.A., Wetterau J.R. Nature 365:65-69(1993) [PubMed: 8361539] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Liver.
[3]	"Human microsomal triglyceride transfer protein large subunit gene structure." Sharp D., Ricci B., Kienzle B., Lin M.C., Wetterau J.R. Biochemistry 33:9057-9061(1994) [PubMed: 7545943] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Kidney.
[5]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[6]	"Transcriptional regulation of human and hamster microsomal triglyceride transfer protein genes. Cell type-specific expression and response to metabolic regulators." Hagan D.L., Kienzle B., Jamil H., Hariharan N. J. Biol. Chem. 269:28737-28744(1994) [PubMed: 7961826] [Abstract] Cited for: TISSUE SPECIFICITY, INDUCTION.
[7]	"The abetalipoproteinemia gene is a member of the vitellogenin family and encodes an alpha-helical domain." Shoulders C.C., Narcisi T.M.E., Read J., Chester S.A., Brett D.J., Scott J., Anderson T.A., Levitt D.G., Banaszak L.J. Nat. Struct. Biol. 1:285-286(1994) [PubMed: 7664034] [Abstract] Cited for: SIMILARITY TO VITELLOGENINS.
[8]	"Mutations of the microsomal triglyceride-transfer-protein gene in abetalipoproteinemia." Narcisi T.M.E., Shoulders C.C., Chester S.A., Read J., Brett D.J., Harrison G.B., Grantham T.T., Fox M.F., Povey S., de Bruin T.W.A., Erkelens D.W., Muller D.P.R., Lloyd J.K., Scott J. Am. J. Hum. Genet. 57:1298-1310(1995) [PubMed: 8533758] [Abstract] Cited for: MUTAGENESIS OF CYS-878.
[9]	"A novel abetalipoproteinemia genotype. Identification of a missense mutation in the 97-kDa subunit of the microsomal triglyceride transfer protein that prevents complex formation with protein disulfide isomerase." Rehberg E.F., Samson-Bouma M.-E., Kienzle B., Blinderman L., Jamil H., Wetterau J.R., Aggerbeck L.P., Gordon D.A. J. Biol. Chem. 271:29945-29952(1996) [PubMed: 8939939] [Abstract] Cited for: VARIANT ABL HIS-540, VARIANTS GLN-297 AND ALA-384, MUTAGENESIS OF ARG-540.
[10]	"Microsomal triglyceride transfer protein (MTP) gene mutations in Canadian subjects with abetalipoproteinemia." Wang J., Hegele R.A. Hum. Mutat. 15:294-295(2000) [PubMed: 10679949] [Abstract] Cited for: VARIANTS ABL HIS-540; ILE-590 AND GLU-746.
[11]	"Novel mutations in the microsomal triglyceride transfer protein gene causing abetalipoproteinemia." Ohashi K., Ishibashi S., Osuga J., Tozawa R., Harada K., Yahagi N., Shionoiri F., Iizuka Y., Tamura Y., Nagai R., Illingworth D.R., Gotoda T., Yamada N. J. Lipid Res. 41:1199-1204(2000) [PubMed: 10946006] [Abstract] Cited for: VARIANT ABL TYR-780.
[12]	"Variants of the microsomal triglyceride transfer protein gene are associated with plasma cholesterol levels and body mass index." Ledmyr H., Karpe F., Lundahl B., McKinnon M., Skoglund-Andersson C., Ehrenborg E. J. Lipid Res. 43:51-58(2002) [PubMed: 11792722] [Abstract] Cited for: VARIANTS HIS-95; THR-128; GLU-244 AND GLN-297.
[13]	"Hypobetalipoproteinemia with an apparently recessive inheritance due to a 'de novo' mutation of apolipoprotein B." Lancellotti S., Di Leo E., Penacchioni J.Y., Balli F., Viola L., Bertolini S., Calandra S., Tarugi P. Biochim. Biophys. Acta 1688:61-67(2004) [PubMed: 14732481] [Abstract] Cited for: VARIANTS THR-128; ILE-168 AND GLN-297.
+	Additional computationally mapped references.

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Cross-references

Sequence databases
	X75500 mRNA. Translation: CAA53217.1. X59657 mRNA. Translation: CAA42200.1. X83013 X83030 Genomic DNA. Translation: CAA58142.1. AK290793 mRNA. Translation: BAF83482.1. BC125110 mRNA. Translation: AAI25111.1. BC125111 mRNA. Translation: AAI25112.1.
IPI	IPI00296645.
PIR	I38047.
RefSeq	NP_000244.2.
UniGene	Hs.195799
3D structure databases
ModBase	Search...
Protein-protein interaction databases
STRING	P55157.
Proteomic databases
PRIDE	P55157.
Genome annotation databases
Ensembl	ENST00000265517; ENSP00000265517; ENSG00000138823; Homo sapiens. [Genome view] ENST00000457717; ENSP00000400821; ENSG00000138823; Homo sapiens. [Genome view]
GeneID	4547.
KEGG	hsa:4547.
UCSC	uc003hvc.2. human.
Organism-specific databases
CTD	4547.
GeneCards	GC04P100715.
H-InvDB	HIX0031471.
HGNC	HGNC:7467. MTTP.
MIM	157147. gene. 200100. phenotype.
Orphanet	14. Abetalipoproteinemia/ homozygous familial hypobetalipoproteinemia.
PharmGKB	PA246.
GenAtlas	Search...
Phylogenomic databases
HOVERGEN	P55157.
OMA	GLEFIST
OrthoDB	EOG9XD69P
Enzyme and pathway databases
Reactome	REACT_602. Metabolism of lipids and lipoproteins.
Gene expression databases
ArrayExpress	P55157.
Bgee	P55157.
CleanEx	HS_MTTP.
Genevestigator	P55157.
GermOnline	ENSG00000138823. Homo sapiens.
Family and domain databases
InterPro	IPR015819. Lipid_transp_b-sht_shell. IPR001747. Lipid_transpt_N. IPR015816. Vitellinogen_b-sht_N. IPR011030. Vitellinogen_superhlx. [Graphical view]
Gene3D	G3DSA:2.30.230.10. Vitellinogen_b-sht_N. 1 hit. G3DSA:1.25.10.20. Vitellinogen_superhlx. 1 hit.
Pfam	PF01347. Vitellogenin_N. 1 hit. [Graphical view]
SMART	SM00638. LPD_N. 1 hit. [Graphical view]
PROSITE	PS51211. VITELLOGENIN. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
DrugBank	DB01094. Hesperetin.
NextBio	17529.
SOURCE	Search...

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Entry information

Entry name

MTP_HUMAN

Accession

Primary (citable) accession number: P55157
Secondary accession number(s): A8K428, Q08AM4

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	October 1, 1996
Last modified:	November 24, 2009
This is version 86 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

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Relevant documents

Human chromosome 4

Human chromosome 4: entries, gene names and cross-references to MIM

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

SIMILARITY comments

Index of protein domains and families

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Sequence annotation (Features)

Molecule processing

Regions

Natural variations

Experimental info

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

Proteomic databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Gene expression databases

Family and domain databases

Other Resources

Entry information

Relevant documents